CRTE7A2-01 TCR-T Cell for HPV-16 Positive Advanced Cervical, Anal, or Head and Neck Cancers

Phase 1

Recruiting

• Conditions: Anal Cancer; Cervical Cancer; Head and Neck Cancers
• Interventions: Drug: Fludarabine + Cyclophosphamide; Drug: Interleukin-2; Biological: CRTE7A2-01 TCR-T Cell

• Registration Number: NCT05122221
• Lead Sponsor: Corregene Biotechnology Co., Ltd

Brief Summary

A single center, open, single arm dose escalation phase I study to evaluate the safety, tolerability, and efficacy of CRTE7A2-01 TCR-T cell for HPV16 positive advanced cervical, anal, or head and neck cancers. The study will determine MTD of CRTE7A2-01 TCR-T cell injection, as well as investigate RP2D.

Detailed Description

Not available

Study Timeline

• Status Verified: 2021-11
• Study First Submitted: 2021-11-05
• Study First Submitted QC: 2021-11-05
• Study First Posted: 2021-11-16
• Last Update Submitted: 2022-06-22
• Last Update Posted: 2022-06-28
• Study Start: 2022-07-17
• Primary Completion: 2023-03
• Study Completion: 2024-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

1. Age ≥18 years and ≤65 years.
2. Histologically-confirmed cervical cancer, anal cancer, head and neck cancers with confirmed HPV16 infection and HLA-A*02:01 allele
3. Failure on or intolerance to systemic therapy for unresectable advanced cancer.
4. ECOG performance status of 0-1.
5. Estimated life expectancy ≥ 3 months.
6. Patients must have at least one measurable lesion defined by RECIST 1.1.
7. Female patients of childbearing age must undergo a serum pregnancy test within 7 days prior to study treatment and the results must be negative, and are willing to use a very effective and reliable method of contraception from screening through 6 months after the last dose of study treatment.
8. The patient must be willing to sign the informed consent form and have a good anticipation of compliance with study procedure.

Exclusion Criteria：

1. The proportion of T cell immune-related gene deletion mutations>5%.

2. Patient received any genetically modified T cell therapy.

3. Patient who is being treated with T cell immunosuppressive agent （such as cyclophosphamide, FK506,tripterygium glycosides） or T cell immunoagonist.

4. Patients received chemotherapy, targeted therapy, immunotherapy, or other investigational agents within 2 weeks and received radiotherapy within 4 weeks before apheresis.

5. Patients with any organ dysfuntion as defined below:

   • leukocytes<3.0 x 109/L
   • absolute neutrophil count >1.5 x 109/L
   • hemoglobin<90g/L
   • platelets <100 x 1010/L
   • lymphocytes<0.8 x 109/L
   • percentage of lymphocytes<15%
   • creatinine>1.5×ULN or creatinine clearance <50mL/min
   • total bilirubin>3×ULN; ALT/AST>3×ULN (patients with liver metastasis,>5×ULN)
   • INR>1.5×ULN; APTT>1.5×ULN
   • SpO2≤90%

6. Patients with serious medical conditions, disorders, and / or comorbidities, including, but are not limited to: severe heart disease, cerebrovascular disease, epileptic seizures, uncontrolled diabetes (CTCAE 5.0: FBG ≥ 2 grade), active infection, active digestive tract Ulcer, gastrointestinal bleeding, intestinal obstruction, pulmonary fibrosis, renal failure, respiratory failure.

7. Patient with a severe cardiovascular disease with 6 months before screening, including, but are not limited to, myocardial infarction, severe or unstable angina, coronary or peripheral artery bypass grafting, Heart failure NYHA grade Ⅲ or Ⅳ.

8. Left Ventricular Ejection Fractions (LVEF) <50%.

9. Patient with a known active brain metastases.

10. Patient with a known myelodysplastic syndrome (MDS) or lymphoma.

11. Patient with a known active autoimmune disease, including , but are not limited to, acquired or congenital immunodeficiency disease, allogeneic organ transplantation, autoimmune hepatitis, systemic lupus erythematosus, inflammatory bowel disease.

12. Patient with a known active Hepatitis B or Hepatitis C.

13. Patient with a history of Human Immunodeficiency Virus (HIV) .

14. Patient with a history of syphilis.

15. Pregnant or lactating women.

16. Patient with a known active mental and neurological diseases.

17. The principal investigator judged that it is not suitable to participate in this clinical study.

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CRTE7A2-01 TCR-T cell therapy	CRTE7A2-01 TCR-T Cell	Patients will undergo lymphocytapheresis, then treatment with TCR-T cell (at escalating doses) + IL-2
CRTE7A2-01 TCR-T cell therapy	Fludarabine + Cyclophosphamide	Patients will undergo lymphocytapheresis, then treatment with TCR-T cell (at escalating doses) + IL-2
CRTE7A2-01 TCR-T cell therapy	Interleukin-2	Patients will undergo lymphocytapheresis, then treatment with TCR-T cell (at escalating doses) + IL-2

Primary Outcome Measures

Name	Time	Method
DLT	28 days	Dose-limiting toxicity
RP2D	28 days	Recommended Phase II Dose
Incidence of treatment related AEs, AEs of special interest and serious adverse events (SAEs).	2 years	grade 1-5 (CTCAE)
MTD	28 days	Maximum Tolerated Dose

Secondary Outcome Measures

Name	Time	Method
Duration of Response（DOR）	2 years	Assessed by RECIST 1.1
Disease Control Rate（DCR）	2 years	Assessed by RECIST 1.1
Progression-Free Survival（PFS）	2 years	Assessed by RECIST 1.1
Objective Response Rate（ORR）	2 years	Assessed by RECIST 1.1

Trial Locations

Locations (1)

The First Affiliated Hospital of Zhengzhou University; 🇨🇳 Zhengzhou, Henan, China